LFA-1-mediated adhesion is regulated by cytoskeletal restraint and by a Ca2+-dependent protease, calpain.
The activity of integrins on leukocytes is kept under tight control to avoid inappropriate adhesion while these cells are circulating in blood or migrating through tissues. Using lymphocyte function-associated antigen-1 (LFA-1) on T cells as a model, we have investigated adhesion to ligand intercellular adhesion molecule-1 induced by the Ca2+ mobilizers, ionomycin, 2, 5-di-t-butylhydroquinone, and thapsigargin, and the well studied stimulators such as phorbol ester and cross-linking of the antigen-specific T cell receptor (TCR)-CD3 complex. We report here that after exposure of T cells to these agonists, integrin is released from cytoskeletal control by the Ca2+-induced activation of a calpain-like enzyme, and adhesive contact between cells is strengthened by means of the clustering of mobilized LFA-1 on the membrane. We propose that methods of leukocyte stimulation that cause Ca2+ fluxes induce LFA-1 adhesion by regulation of calpain activity. These findings suggest a mechanism whereby engagement of the TCR could promote adhesion strengthening at an early stage of interaction with an antigen-presenting cell.
Stewart
M P
MP
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
McDowall
A
A
Hogg
N
N
D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology; D047630:Depsipeptides; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000502:physiology*; D018613:Microscopy, Confocal; D010456:Peptides, Cyclic / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology
D047630:Depsipeptides; D006873:Hydroquinones; D016169:Lymphocyte Function-Associated Antigen-1; D010456:Peptides, Cyclic; C057531:jasplakinolide; D018799:Intercellular Adhesion Molecule-1; C019359:2,5-di-tert-butylhydroquinone; D015759:Ionomycin; D019284:Thapsigargin; D002154:Calpain; D002118:Calcium